Neuroblastoma is a neoplasm known to show spontaneous histologic maturation in vivo which correlates with a better biologic behavior and prognosis. Extracellular matrix (ECM) proteins, on the other hand, have been shown to influence tumor invasion and metastasis. Production of ECM proteins has been previously reported only for the C1300 murine neuroblastoma cell line. We have studied ECM synthesis in relation to differentiation of human neuroblastoma in vitro. Differentiation was induced by dibutyryl-cyclic AMP and retinoic acid. Morphologic differentiation has also been studied by electron microscopy and will be correlated with differences in biochemical expression of neurotransmitter enzymes. In the present project, we will assess qualitative and quantitative differences in ECM protein synthesis by neuroblastomas in vitro before and after differentiation by immunofluorescence and polyacrylamide gel electrophoresis. The differences will then be correlated with maxtrix degradation and invasion in vitro, employing a human amnion invasion assay. Preliminary data show that differentiating neuroblastoma is associated with increased fibronectin synthesis and decreased in vitro invasiveness. Neuroblastoma is an especially useful model of biological control of malignancy, since it has the highest rate of spontaneous regression of any tumor, and this is correlated with differentiation. Study of the expression of ECM proteins and their degradation with in vitro invasiveness will hopefully elucidate various aspects of the biologic control of invasion and metastasis.